1. Field of the Invention
This invention relates generally to degradable polymers. More particularly, the invention relates to crosslinked cationic polymers in which the crosslinks are degradable under physiological conditions. Preferred degradable cationic polymers are useful for delivering bioactive materials (such as nucleic acids) into the nuclei of cells.
2. Description of the Related Art
Gene therapy involves the delivery of nucleic acids (such as DNA) to the nuclei of cells. Both viral and non-viral delivery systems have been developed (1–5). Advantages of non-viral delivery systems include nonimmunogenicity, low acute toxicity, and design flexibility (6–10). A variety of materials have been developed as non-viral gene carriers, including cationic lipids and liposomes (11), endosomal lysis peptides (12), and polymers such as poly-L-lysine (PLL) and its conjugates (13), polyethyleneimine (PEI) (14), polyamidoamine (PAMAM) dendrimers (15), and poly[α-(4-aminobutyl)-L-glycolic acid] (PAGA) (16).
Non-viral gene delivery systems typically function by: (a) formation of a complex between the gene carrier and a nucleic acid, (b) uptake of the complex by cells via endocytosis, (c) escape of the nucleic acid from the endosomes, and (d) entry of the nucleic acid into the nuclei (23). Biodegradable polymer gene carriers have been developed to reduce any potential cytotoxicity of the gene carrier that remains (17–22). However, existing biodegradable polymer gene carriers suffer from a number of shortcomings. For example, such carriers often tend to degrade too slowly (thus risking damage to tissue) or remain inside the cytoplasm for only a short time, resulting in incomplete delivery of the nucleic acid.